Frequent Sequence Variation in the Human Myostatin (GDF8) Gene as a Marker for Analysis of Muscle-Related Phenotypes

Ferrell, Robert E.; Conte, Victor; Lawrence, Elizabeth; Roth, Stephen M.; Hagbèrg, James M.; Hurley, Ben F.

doi:10.1006/geno.1999.5984

Cited by 103 publications

(129 citation statements)

References 26 publications

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“…Recent research from our laboratory showed that heterozygosity for this variation can alter the functional capacity of adult women, yet their muscle function was already altered by an inherited myopathy (Gonzalez-Freire et al 2009). Although more research is needed, the GDF8 K153R polymorphism has the potential to alter the function of the GDF8 gene (Ferrell et al 1999;Saunders et al 2006), as briefly explained below. Myostatin enters the bloodstream as a latent precursor protein and then undergoes a proteolytic process to become a mature peptide (free from the propeptide) that binds to extracellular activin type II receptor (ActRIIB) (Kostek et al 2009).…”

Section: Resultsmentioning

confidence: 99%

“…Of the identified polymorphisms, the Lys(K)153Arg(R) variation located in exon 2 (rs1805086, 2379 A>G replacement) is a candidate to influence skeletal muscle phenotypes. The frequency of the mutant R allele is of about 3-4% among Caucasians, with a frequency of mutant homozygotes (RR) below 1% (Corsi et al 2002;Ferrell et al 1999;Kostek et al 2009). Such low allelic frequency certainly limits the possibility of studying large groups of people carrying the R variant.…”

Section: Introductionmentioning

confidence: 99%

“…Such low allelic frequency certainly limits the possibility of studying large groups of people carrying the R variant. Though controversy exists with regards to adults (Kostek et al 2009), the K153R polymorphism is associated with muscle strength, with the infrequent mutant R allele possibly exerting a negative influence in old (yet <80 years) Caucasian people (Ferrell et al 1999;Huygens et al 2004;Seibert et al 2001).…”

Section: Introductionmentioning

confidence: 99%

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The K153R variant in the myostatin gene and sarcopenia at the end of the human lifespan

González-Freire

Rodríguez-Romo

Santiago

et al. 2010

AGE

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We studied the A55T, E164K, I225T, K153R and P198A variants in the myostatin (GDF8) gene, muscle strength and mass, and physical function during daily living in 41 nonagenarians [33 women, age range, 90, 97]. No participant carried a mutant allele of the aforementioned variants, except three participants (all women), who carried the R allele of the K153R polymorphism, with one of them (woman aged 96 years) being homozygous. Overall, in KR women muscle phenotype values (1RM leg press and estimated muscle mass) were low-to-normal compared to the whole group (∼25th-50th percentile), and their functional capacity (Barthel and Tinetti tests) was normal. In the woman bearing the RR genotype, values of muscle mass and functional capacity were below the 25th percentile. She is the first RR Caucasian whose phenotype has been characterised specifically. In summary, heterozygosity for the GDF8 K153R polymorphism does not seem to exert a negative influence on the muscle phenotypes of women who are at the end of the human lifespan, yet homozygosity might do so. More research on larger cohorts of nonagenarians is needed to corroborate the present findings.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The K153R variant in the myostatin gene and sarcopenia at the end of the human lifespan

González-Freire

Rodríguez-Romo

Santiago

et al. 2010

AGE

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“…Genotyping of the K153R polymorphism was performed in the Italian cohort during November 2012. The procedure for detecting the K153R polymorphism was based on PCR amplification, restriction cleavage with BanII (New England Biolabs, Ipswich, MA, USA) and separation of the DNA fragments by electrophoresis, as previously described (Ferrell et al 1999). For quality control, genotyping analyses were done blind with respect to centenarian/young control status, and a random 25 % of the samples were repeated.…”

Section: Genotype Assessmentmentioning

confidence: 99%

“…Of the identified MSTN variations in humans, the Lys (K)153Arg(R) polymorphism located in exon 2 (rs1805086, 2379 A>G replacement) is one candidate to influence skeletal muscle phenotypes (Ferrell et al 1999). The Lys(K)153Arg(R) amino acid replacement is found within the active mature peptide of the myostatin protein; it could influence proteolytic processing with its pro-peptide or affinity to bind with the extracellular activin type II receptor (ActRIIB).…”

Section: Introductionmentioning

confidence: 99%

Association of the K153R polymorphism in the myostatin gene and extreme longevity

Garatachea

Pinós

Cámara

et al. 2013

AGE

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The myostatin (MSTN) gene is a candidate to influence extreme longevity owing to its role in modulating muscle mass and sarcopenia and especially in inhibiting the main nutrient-sensing pathway involved in longevity, i.e. mammalian target of rapamycin. We compared allele/genotype distributions of the exonic MSTN variants K153R (rs1805086), E164K (rs35781413), I225T and P198A, in Spanish centenarians (cases, n=156; 132 women, age range 100-111 years) and younger adults (controls, n=384; 167 women, age <50 years). No subject of either group carried a mutant allele of the E164K, I225T or AGE (2013) 35:2445-2454 DOI 10.1007 Antoni L. Andreu and Alejandro Lucia share senior authorship. P198A variation. The frequency of the variant R allele was significantly higher in centenarians (7.1 %) than in controls (2.7 %) (P=0.001). The odds ratio of being a centenarian if the subject had the R allele was 3.48 (95 % confidence interval 1.67-7.28, P=0.001), compared to the control group, after adjusting for sex. The results were replicated in an Italian cohort (centenarians, n=79 (40 women), age range 100-104 years; younger controls, n=316 (155 women), age <50 years), where a higher frequency of the R allele in centenarians (7.6 %) compared to controls (3.0 %) (P=0.004) was independently confirmed. Although more research is needed, the variant allele of the MSTN K153R polymorphism could be among the genetic contributors associated with exceptional longevity.

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Genes and Strength and Power Phenotypes

Thomis

2010

Genetic and Molecular Aspects of Sport Performance

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Frequent Sequence Variation in the Human Myostatin (GDF8) Gene as a Marker for Analysis of Muscle-Related Phenotypes

Cited by 103 publications

References 26 publications

The K153R variant in the myostatin gene and sarcopenia at the end of the human lifespan

The K153R variant in the myostatin gene and sarcopenia at the end of the human lifespan

Association of the K153R polymorphism in the myostatin gene and extreme longevity

Genes and Strength and Power Phenotypes

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